Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors: Part I. Synthesis and Structure-Activity Relationship of 1-Alkoxymethyl-5-alkyl-6-naphthylmethyl Uracils as HEPT Analogues

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概要

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• 1-Alkoxymethyl-5-alkyl-6-naphthylmethyl uracils, which are novel 1-[(2-hydroxyethoxy)methyl|-6-(phenylthio)thymine (HEPT) analogues, were synthesized for evaluation as selective and potent nonnucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitors. The anti-HIV-1 activity of these compounds was assayed in vitro using HIV-1 infected MT-4 and CEM bioassays. The EC_<50>, CC_<50> and SI were recorded and calculated. The appropriate position, especially in the 1-position of the naphthyl ring, led to dramatic increases in potency, in both MT-4 and CEM cellular assays. The most important compounds in this series,1-ethoxymethyl-5-isopropyl-6-(1-naphthylmethyl)thymine 81 (IC_<50>=17nM, CC_<50>=38332 nM, SI=2229) and 1-benzyloxymethyl-5-ethyl-6-(1-naphthylmethyl)thymine 8n (IC_<50>=17nM, CC_<50>=32560nM, SI = 1889) were significantly more potent than HEPT (EC_<50>=7.0μM, CD_<50>=740μM) in the anti-HIV-1 in vitro cellular assay.

• 社団法人日本薬学会の論文
• 2003-07-01

著者

• De Clercq

  Rega Inst. For Medical Res. Katholieke Universiteit Leuven

• BALZARINI Jan

  Rega Institute for Medical Research, Katholieke Universiteit Leuven

• PANNECOUQUE Christophe

  Rega Institute for Medical Research, Katholieke Universiteit Leuven

• MENG Ge

  Department of Chemistry, Fudan University

• CHEN Fen-Er

  Department of Chemistry, Fudan University

• Blanco Jose

  Departamento De Farmacologia Facultade De Farmacia Universidade De Santiago De Compostela

• Balzarini J

  Rega Inst. For Medical Res.

• Chen Fen-er

  Dep. Of Chemistry Fudan Univ.

• Chen Fen-er

  Department Of Chemistry Fudan University

• Pannecouque Christophe

  Rega Instituut Katholieke Universiteit Leuven

• Pannecouque C

  Katholieke Univ. Leuven Leuven Bel

• Balzarini Jan

  Rega Inst. For Medical Res.

• Balzarini J

  Rega Institute For Medical Research Katholieke Universiteit Leuven

• Meng Ge

  Department Of Chemistry Fudan University

• Pannecouque Christophe

  Rega Inst. For Medical Res. Katholieke Universiteit Leuven

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